ALDARA - ALDARA - CT 7369 - English version

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Description

Introduction ALDARA 5%, cream Box of 12 250 mg single-use sachets (CIP: 349 204-4) Posted on May 30 2011 Active substance (DCI) imiquimod ATC Code D06BB10 Laboratory / Manufacturer MEDA PHARMA ALDARA 5%, cream Box of 12 250 mg single-use sachets (CIP: 349 204-4) Posted on May 30 2011

Informations

• Publié par: haute-autorite-sante-maladies-appareil-genital
• Publié le: 10 mars 2010
• Nombre de lectures: 24
• Licence : En savoir +
  Paternité, pas d'utilisation commerciale, partage des conditions initiales à l'identique
• Langue: English

Extrait

The legally binding text is the original French version

TRANSPARENCY COMMITTEE

OPINION

10 March 2010



Review of the dossier of the proprietary drug included on the list of reimbursable products for
a period of 5 years as from 4 May 2005 (JO of 9 August 2005)

ALDARA 5%, cream
Box of 12 250 mg single-use sachets (CIP: 349 204-4)


Applicant: MEDA PHARMA

Imiquimod

ATC code: D06BB10

List I

Date of Marketing Authorisation: 18/09/1998 (indication for external genital warts)
Amendment dated 13/07/2004: extension of indication to basal cell carcinomas
Amendment dated 24/04/2007: extension of indication to actinic keratoses



Reason for the request: Renewal of inclusion on the list of medicines reimbursed by National
Health Insurance.















Medical, Economic and Public Health Assessment Division
1 1 CHARACTERISTICS OF THE MEDICINAL PRODUCT

1.1. Active ingredient
Imiquimod

1.2. Indications
“Imiquimod is indicated for the topical treatment of:
- external genital and perianal warts (condylomata acuminata) in adults.
- small superficial basal cell carcinomas (sBCCs) in adults.
- clinically typical, non-hypertrophic, non-hyperkeratotic actinic keratoses (AKs) on the
face or scalp in immunocompetent adult patients when size or number of lesions limit the
efficacy and/or acceptability of cryotherapy and other topical treatment options are
contraindicated or less appropriate.”

1.3. Dosage
The application frequency and duration of treatment with imiquimod cream are different for
each indication.

“External genital warts in adults: imiquimod cream should be applied 3 times per week
(example: Monday, Wednesday and Friday; or Tuesday, Thursday and Saturday) prior to
normal sleeping hours and should remain on the skin for 6 to 10 hours. Imiquimod cream
treatment should continue until the clearance of visible genital or perianal warts or for a
maximum of 16 weeks per episode of warts.

Superficial basal cell carcinoma in adults: apply imiquimod cream for 6 weeks, 5 times per
week (example: Monday to Friday) prior to normal sleeping hours, and leave on the skin for
approximately 8 hours.

Actinic keratosis in adults: treatment should be initiated and monitored by a physician.
Imiquimod cream should be applied 3 times per week (example: Monday, Wednesday and
Friday) for four weeks prior to normal sleeping hours, and left on the skin for approximately 8
hours. Sufficient cream should be applied to cover the treatment area. After a 4-week
treatment-free period, clearance of AKs should be assessed. The maximum recommended
dose is one sachet. The maximum recommended treatment duration is 8 weeks. An
interruption of dosing should be considered if intense local inflammatory reactions occur or if
infection is observed at the treatment site. In this latter case, appropriate other measures
should be taken. Each treatment period should not be extended beyond 4 weeks due to
missed doses or rest periods. If the treated lesion(s) show an incomplete response at the
follow-up examination at 4-8 weeks after the second treatment period, a different therapy
should be used.”

2
2 REMINDER OF THE COMMITTEE"S OPINIONS AND CONDITIONS OF
INCLUSION


Opinion of the Committee of 3 November 1999

External perianal and genital warts (condylomata acuminata) in adults:
Analysis of clinical trials on the drug and comparative data
The efficacy of ALDARA versus placebo has been clearly demonstrated. The product is well
tolerated apart from localised skin reactions.
A meta-analysis of published studies into various forms of therapeutic management has
been added to the dossier. The methodology is imperfect and does not allow the proprietary
drug ALDARA cream to be clearly positioned in respect of the alternative treatments.
The following points should be underlined:
- experience with the use of ALDARA cream to treat foreskin warts in uncircumcised men is
limited. Data from patients in this category using ALDARA three times a week and
cleaning their foreskin daily related to fewer than 100 patients.
- repeat-treatment following the recurrence of warts has not been investigated; therefore,
repeat-treatment is not recommended.
- ALDARA is less effective in removing condylomata among HIV-positive patients, although
limited data has shown a statistically significant difference versus placebo in one of the
secondary efficacy endpoints (rate of partial reduction in condylomata size).

Actual benefit
This proprietary drug is intended to provide curative treatment.
It should have a prominent position in the treatment strategy for this condition. This position
needs to be confirmed by studies comparing the product to other drugs treatments and
surgery. Furthermore, the efficacy and tolerance of ALDARA cream have not been
sufficiently evaluated in HIV-positive patients or in uncircumcised male patients undergoing
repeat-treatment after the recurrence of warts.
The actual benefit of this proprietary drug is high.

Improvement in actual benefit
Though no comparative studies versus other drug treatments have been carried out, the
Committee is of the opinion that ALDARA represents a minor improvement in actual benefit
(level IV) in terms of ease of use (one application per day rather than two applications per
day) compared to the proprietary product CONDYLINE solution for local application.

Recommended therapeutic strategy
Doctors use a variety of therapeutic strategies: drug treatments (including podophyllin
preparations made up in the pharmacy) or ablative procedures (removal by surgery,
cryotherapy, laser or electrocauterisation). No consensus position has been established as to
the best strategy for this condition.

Opinion of the Committee of 13 April 2005
Renewal of inclusion:
Actual benefit
External perianal and genital warts (condylomata acuminata) in adults are caused by a
sexually transmissible viral infection.
Their recurrence is a major problem in this infection.
The efficacy/adverse effect ratio of ALDARA 5% cream is high.
It is intended for curative treatment.
3 The actual benefit of ALDARA 5% cream is substantial.

Treatment strategy
1 2New guidelines have been published in Europe and the USA since the Transparency
Committee"s last opinion. These guidelines place treatments in two categories: those
administered by a doctor (surgery, laser treatment, cryotherapy, trichloroacetic acid) and
those which can be applied by the patient (imiquimod, podophyllotoxin).
Most condylomata acuminata are suitable for treatment with any of these options, which can
be used in the case of the initial infection or in the event of relapse. In view of the fact that no
therapeutic strategy results in a complete cure of the condylomata acuminata, and that the
various treatments offered have identical levels of proof of efficacy, there is no consensus as
to which of the various options available (drug treatments and ablative procedures) should be
preferred in terms of treatment strategy. The choice of treatment, particularly in the case of
imiquimod, therefore depends on the nature of the lesions, the practitioner"s experience and
the patient"s preference.

Improvement in actual benefit
ALDARA 5% cream is still a useful additional therapeutic option the overall management
strategy for condylomata acuminata in adults.


Opinion of the Committee of 16 March 2005
Small basal cell carcinomas in adults:
Actual benefit
Basal cell carcinomas are tumours whose malignancy is essentially local, are slow to
develop, and are very rarely life-threatening.
Among the forms which have been frequently described on the basis of clinical and
histological criteria, small superficial basal cell carcinomas which are not located near
the facial orifices are regarded as having a good prognosis in respect of the risk of
relapse.
The efficacy and tolerance of ALDARA 5% cream have been demonstrated in placebo-
controlled studies on small superficial tumours. No data is currently available to assess
the long-term efficacy of imiquimod. No data is available to describe the mode of
superficial or deep relapse.
There is no alternative drug treatment, as ALDARA 5% cream is the only proprietary
drug indicated for small superficial basal cell carcinoma. The only possible alternative is
a non-drug treatment: surgery is the treatment of choice that should be offered as first-
line treatment. If surgery is contraindicated, other techniques such as cryosurgery,
radiotherapy and electrocoagulation can be suggested.
Public health benefit:
In terms of public health, the burden represented by small superficial basal cell
carcinomas in adults is low as this cancer has a good prognosis (relapse is rare and it
is never fatal) and the target population (patients for whom surgery is contraindicated)
is small (fewer than 7,000 patients).
The only alternatives available f